This invention relates to techniques for minimizing percutaneous absorption of toxic chemicals and for effective removal of toxic chemicals from skin or other surfaces exposed to the chemicals.
Skin exposure to toxic chemicals has long been a problem. To prevent skin exposure to chemicals, gloves or other protective clothing have been worn. Such gloves, however, are cumbersome to wear and have caused allergic reactions and other problems.
Heretofore, when non-protected skin was contacted with harmful toxic chemicals (“contaminant chemicals”), the skin would typically be flushed with copious amounts of water or with soap and water (as routinely recommended by most material safety data sheets) to try to cleanse the skin of the contaminant chemical and prevent percutaneous absorption thereof. Though this may have been useful for skin exposed to hydrophilic chemicals, it was not efficient for removing from the skin chemicals which are not soluble in water (lipophilic) or only slightly soluble in water (semi-polar). In fact, rinsing with water may actually increase the percutaneous absorption of such chemicals.
Percutaneous absorption and systemic absorption of chemicals is a two step process. The first step is the initial partitioning of a lipophilic chemical into the lipid components in the stratum corneum. This initial absorption can be relatively rapid if the chemical is a strong solvent and of low molecular weight. The process will move more slowly if the chemical is a higher molecular weight or less lipid soluble.
The second step in the systemic absorption process is the partitioning of the chemical from the lipophilic components of the skin into the hydrophilic bloodstream. This process can be quite slow as the preferential solubility of the chemical in the stratum corneum lipids serves to retain the chemical in the skin. This absorbed dose of chemical in the skin is referred to as the skin depot.
The use of water to first wet the skin when attempting to remove toxic lipophilic chemicals has two detrimental effects which can result in an enhancement of percutaneous exposure. First, due to the poor solubility of these chemicals in water, the use of water can spread chemical contamination over a greater surface area of the skin. Thus, percutaneous exposure to the chemical can increase.
Secondly, the application of water to the skin results in a rapid hydration and saturation of the corneocytes (dead skin cells constituting the stratum corneum). The lipophilic chemical already absorbed into the skin's lipids (skin depot) is now presented with a very different solubility environment. Where a lipophilic chemical previously demonstrated a higher preferential solubility in the skin lipids as opposed to the hydrophilic bloodstream; the hydration of the skin with water now shifts the skin to a hydrophilic state. Thus, the absorbed chemical is more rapidly absorbed into the body as its solubility in the skin decreases. Partitioning into the bloodstream now becomes concentration rather than solubility dependent.
Therefore, the use of water or soap and water can increase the area of skin exposure and cause a more rapid systemic absorption of the chemical into the bloodstream.
Though it is known that common lipophilic chemicals are more soluble in lipophilic solvents than water, the application of common lipophilic solvents to the skin to remove contaminant chemicals therefrom has not been successful because, as discussed below, these solvents penetrate or diffuse across the skin and allow the contaminant chemical to be carried across the skin barrier.
The ability of a chemical to be absorbed through the skin depends on two primary chemical characteristics, its solubility relative to water and its molecular size.
The outermost layer of the skin, the stratum corneum, consists mainly of highly keratinized dead skin cells held together by interstitial layers of lipids. The primary function of the stratum corneum is to retain moisture in the body and provide a physical barrier to infectious bacteria and viruses. Thus, the skin is a highly effective barrier to the absorption or loss of water and water soluble (hydrophilic) chemicals.
The ability, or lack thereof, of a chemical to partition into the stratum corneum is the initial limiting step in determining the dermal penetration rate (Kp). Since like materials dissolve like materials, the stratum corneum is most permeable to fat soluble (lipophilic) chemicals because of its layers of lipids.
The second characteristic determining the dermal penetration rate (Kp) is the molecular size of the chemical contaminant. Molecular size generally increases with the molecular weight (MW) of the chemical. Chemicals with high molecular weights, such as those greater than 350, are significantly limited in their ability to permeate the stratum corneum due to their physical size, while lower molecular weight chemicals more easily permeate the stratum corneum.
Thus, low molecular weight lipophilic chemicals that are insoluble or poorly soluble in water are readily absorbed through the skin.
Solvents for removing contaminant chemicals from the skin should be chosen based on their ability to dissolve those chemicals. The solubility of a chemical in a solvent is determined by it octanol/water partition coefficient (log K o/w). Solvents with a log K o/w value similar to that of a contaminant chemical will readily dissolve the chemical.
An appropriate solvent is important because the partition coefficient of a contaminant chemical, Ksc/Kv (Ksc, solubility in the stratum corneum, vs Kv, solubility in the solvent), defines the equilibrium ratio of the concentration of the compound in the stratum corneum to that in the adjacent application solvent (trying to dissolve the chemical). Therefore, a contaminant chemical with a higher affinity (solubility) for a solvent that is applied on the skin will partition more slowly into the stratum corneum. Therefore, one would believe that solvents which readily dissolve a contaminant chemical would, when applied to skin contacted with the contaminant, dissolve the contaminant chemical and limit percutaneous absorption thereof.
This concept, however, is valid only if the solvent itself does not affect the absorption properties of the skin (damage the stratum corneum) and if the solvent itself does not diffuse across the stratum corneum. If the solvent does diffuse across the stratum corneum, it acts as a carrier or active transport of the contaminant chemical being absorbed. Therefore, though a contaminant chemical may have a much higher solubility in a low molecular weight lipophilic solvent than in the stratum corneum, the low molecular weight lipophilic solvent could not be used to prevent percutaneous absorption of the chemical because the low molecular weight lipophilic solvent would be absorbed into the stratum corneum and act as a carrier for the chemical.
Disrupting the stratum corneum significantly increases the percutaneous absorption of chemical exposure, thereby contributing to the development of irritant or allergic dermatitis. Thus, skin cleansers incorporating harsh detergents which can damage the skin tend to increase the potential for skin absorption of chemical exposure. The addition of cosmetic emollients or “moisturizers” to such cleansers can further promote chemical absorption. Commonly used additives, such as aloe vera and isoproplymyristate are rapidly absorbed into the stratum corneum. Moreover, these additives have been proven to be effective vehicles to enhance the absorption efficacy of lipohilic drugs. D-limonene, widely employed in citrus-based skin cleansers, has been shown to be among the most effective penetration enhancers for dermal drug delivery.
Thus, to date, there have been no completely satisfactory methods for minimizing the percutaneous absorption of lipophilic or semi-polar chemicals which have been in contact with the skin.
OSHA also recognized that there have been no such satisfactory methods. On Aug. 10, 1992, OSHA promulgated a final rule, 29 CFR, parts 1910 and 1926, Occupational exposure to 4,4′ methylenedianiline (MDA). OSHA recognized in assessing exposure risk that “in certain situations approximately 95% of exposure results from dermal absorption.” OSHA further stated “MDA cannot be completely removed by cleansing. The data suggest that the use of solvents to remove MDA from the skin actually increases the absorption of MDA. It also appears that soap and water provide the best medium for removing the substance from the skin but only removes 60% of the material deposited on the skin.”
The final standard requires that “workers subjected only to dermal exposure to MDA must be instructed to immediately wash exposed areas with soap and water or any medium which does not increase the absorption properties of MDA. This particular requirement was given much consideration by OSHA.”
The comments to the rule make it clear that OSHA did not want to require that only soap and water be used to remove MDA impregnated resin or accumulations on the skin because something better might be developed in the future. OSHA believed that if a particular solvent could be demonstrated not to increase the absorption properties of MDA it should be used to remove MDA from the skin. OSHA, did not, however, suggest any such solvent.
The same chemical principles of solubility apply to the decontamination of chemicals from surfaces of personal protective clothing or equipment (PPE), gloves, suits, respirators, etc. Many items of protective clothing or other equipment may be quite expensive and, therefore, are not discarded after use. It is common practice for firefighters or emergency response personnel, after being exposed to toxic chemicals, to wash their gear with a water rinse shower before removal. This act of apparent decontamination provides a false sense of security that the protective gear is free from contamination during removal and storage. A recent study demonstrated that 90% of workers contaminated their hands when removing and then re-using exposed gloves. Although in this study there was no attempt to decontaminate the gloves prior to removal, standard practices of a water rinse would have invariably left contamination. Ineffective decontamination of PPE may increase exposures if the workers falsely believe their protective equipment is clean. It is therefore apparent that improvements over the standard use of soap and water to decontaminate skin and protective equipment from toxic lipophilic chemicals will significantly improve worker safety.
Sometimes, in certain industrial environments and the like, over time deposits of contaminant materials may build up on a worker's protective equipment, such as gloves. When this occurs, it is known for the worker to simply dip the gloves into a suitable solvent for removing the contaminant material. However, such solvents, particularly if they are of low molecular weight, may be able to penetrate the glove surface and actually serve as a carrier for the contaminant material to the inside of the glove.